Hydroxamates of para-aminobenzoic acid as selective inhibitors of HDAC8

作者：Kulandaivelu Umasankar; Chilakamari Laxmi Manasa; Jadav Surender Singh; Rao Tadikonda Rama; Jayaveera K N; Shireesha Boyapati; Hauser Alexander Thomas; Senger Johanna; Marek Martin; Romier Christophe; Jung Manfred^*; Jayaprakash Venkatesan

来源：Bioorganic Chemistry, 2014, 57: 116-120.

DOI：10.1016/j.bioorg.2014.08.005

• p-Aminobenzoic acid derivatives
• Hydroxamates
• HDAC8
• Inhibitors
• Molecular docking

A series of hydroxamates (4a-4l) were prepared from p-aminobenzoic acid to inhibit HDAC8. The idea is to substitute rigid aromatic ring in place of less rigid piperazine ring of hydroxamates reported earlier by our group. It is expected to increase potency retaining the selectivity. Result obtained suggested that the modifications carried out retained the selectivity towards HDAC8 isoform and increasing the potency in very few cases. Increase in potency is also associated with variation in cap aryl region. Two compounds (4f %26 4l) were found to inhibit HDAC8 at concentrations (IC50) less than 20 mu M.

• 出版日期2014-12